Targeting mitochondrial and cytosolic substrates of TRIT1 isopentenyltransferase: Specificity determinants and tRNA-i6A37 profiles

Autoři: Abdul Khalique aff001;  Sandy Mattijssen aff001;  Alexander F. Haddad aff001;  Shereen Chaudhry aff001;  Richard J. Maraia aff001
Působiště autorů: Intramural Research Program of the National Institute of Child Health and Human Development, of the National Institutes of Health, Bethesda, Maryland, United States of America aff001;  Commissioned Corps, United States Public Health Service, Rockville, Maryland, United States of America aff002
Vyšlo v časopise: Targeting mitochondrial and cytosolic substrates of TRIT1 isopentenyltransferase: Specificity determinants and tRNA-i6A37 profiles. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008330
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008330


The tRNA isopentenyltransferases (IPTases), which add an isopentenyl group to N6 of A37 (i6A37) of certain tRNAs, are among a minority of enzymes that modify cytosolic and mitochondrial tRNAs. Pathogenic mutations to the human IPTase, TRIT1, that decrease i6A37 levels, cause mitochondrial insufficiency that leads to neurodevelopmental disease. We show that TRIT1 encodes an amino-terminal mitochondrial targeting sequence (MTS) that directs mitochondrial import and modification of mitochondrial-tRNAs. Full understanding of IPTase function must consider the tRNAs selected for modification, which vary among species, and in their cytosol and mitochondria. Selection is principally via recognition of the tRNA A36-A37-A38 sequence. An exception is unmodified tRNATrpCCA-A37-A38 in Saccharomyces cerevisiae, whereas tRNATrpCCA is readily modified in Schizosaccharomyces pombe, indicating variable IPTase recognition systems and suggesting that additional exceptions may account for some of the tRNA-i6A37 paucity in higher eukaryotes. Yet TRIT1 had not been characterized for restrictive type substrate-specific recognition. We used i6A37-dependent tRNA-mediated suppression and i6A37-sensitive northern blotting to examine IPTase activities in S. pombe and S. cerevisiae lacking endogenous IPTases on a diversity of tRNA-A36-A37-A38 substrates. Point mutations to the TRIT1 MTS that decrease human mitochondrial import, decrease modification of mitochondrial but not cytosolic tRNAs in both yeasts. TRIT1 exhibits clear substrate-specific restriction against a cytosolic-tRNATrpCCA-A37-A38. Additional data suggest that position 32 of tRNATrpCCA is a conditional determinant for substrate-specific i6A37 modification by the restrictive IPTases, Mod5 and TRIT1. The cumulative biochemical and phylogenetic sequence analyses provide new insights into IPTase activities and determinants of tRNA-i6A37 profiles in cytosol and mitochondria.

Klíčová slova:

Eukaryota – Mitochondria – Northern blot – Point mutation – Saccharomyces cerevisiae – Schizosaccharomyces pombe – Transfer RNA – Anticodons


1. Sokolowski M, Klassen R, Bruch A, Schaffrath R, Glatt S. Cooperativity between different tRNA modifications and their modification pathways. Biochim Biophys Acta. 2017

2. Chatterjee K, Nostramo RT, Wan Y, Hopper AK. tRNA dynamics between the nucleus, cytoplasm and mitochondrial surface: Location, location, location. Biochim Biophys Acta Gene Regul Mech. 2018;1861(4):373–86 doi: 10.1016/j.bbagrm.2017.11.007 29191733

3. Vare VY, Eruysal ER, Narendran A, Sarachan KL, Agris PF. Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function. Biomolecules. 2017;7(1)

4. Suzuki T, Suzuki T. A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs. Nucleic Acids Res. 2014;42(11):7346–57 doi: 10.1093/nar/gku390 24831542

5. Wei FY, Zhou B, Suzuki T, Miyata K, Ujihara Y, Horiguchi H, et al. Cdk5rap1-mediated 2-methylthio modification of mitochondrial tRNAs governs protein translation and contributes to myopathy in mice and humans. Cell Metab. 2015;21(3):428–42 doi: 10.1016/j.cmet.2015.01.019 25738458

6. Lamichhane TN, Arimbasseri AG, Rijal K, Iben JR, Wei FY, Tomizawa K, et al. Lack of tRNA-i6A modification causes mitochondrial-like metabolic deficiency in S. pombe by limiting activity of cytosolic tRNATyr, not mito-tRNA. RNA. 2016;22(4):583–96 doi: 10.1261/rna.054064.115 26857223

7. Schweizer U, Bohleber S, Fradejas-Villar N. The modified base isopentenyladenosine and its derivatives in tRNA. RNA biology. 2017:1–12

8. Chou HJ, Donnard E, Gustafsson HT, Garber M, Rando OJ. Transcriptome-wide Analysis of Roles for tRNA Modifications in Translational Regulation. Mol Cell. 2017;68(5):978–92 e4 doi: 10.1016/j.molcel.2017.11.002 29198561

9. Han L, Phizicky EM. A rationale for tRNA modification circuits in the anticodon loop. RNA. 2018

10. Guy MP, Shaw M, Weiner CL, Hobson L, Stark Z, Rose K, et al. Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicated in Nonsyndromic X-Linked Intellectual Disability due to Mutations in FTSJ1. Hum Mutat. 2015

11. Guy MP, Phizicky EM. Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes. RNA. 2014

12. Arimbasseri AG, Iben J, Wei FY, Rijal K, Tomizawa K, Hafner M, et al. Evolving specificity of tRNA 3-methyl-cytidine-32 (m3C32) modification: a subset of tRNAsSer requires N6-isopentenylation of A37. RNA. 2016;22(9):1400–10 doi: 10.1261/rna.056259.116 27354703

13. Han L, Marcus E, D'Silva S, Phizicky EM. S. cerevisiae Trm140 has two recognition modes for 3-methylcytidine modification of the anticodon loop of tRNA substrates. RNA. 2016;23:406–19 doi: 10.1261/rna.059667.116 28003514

14. Yarham JW, Lamichhane T., Mattijssen S., Bruni F., McFarland R., Maraia R.J., Taylor R.W. Defective i6A37 Modification of Mitochondrial and Cytosolic tRNAs Results from Pathogenic Mutations in TRIT1 and its Substrate tRNA. PLoS Genetics. 2014;Jun 5;10(6):e1004424 doi: 10.1371/journal.pgen.1004424 24901367

15. Kernohan KD, Dyment DA, Pupavac M, Cramer Z, McBride A, Bernard G, et al. Matchmaking facilitates the diagnosis of an autosomal-recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene. Hum Mutat. 2017;38:511–6 doi: 10.1002/humu.23196 28185376

16. Edvardson S, Elbaz-Alon Y, Jalas C, Matlock A, Patel K, Labbe K, et al. A mutation in the THG1L gene in a family with cerebellar ataxia and developmental delay. Neurogenetics. 2016;17(4):219–25 doi: 10.1007/s10048-016-0487-z 27307223

17. Tarnopolsky MA, Brady L, Tetreault M, Care4Rare Canada C. TRMT5 mutations are associated with features of complex hereditary spastic paraparesis. Neurology. 2017;89(21):2210–1 doi: 10.1212/WNL.0000000000004657 29021354

18. Powell CA, Kopajtich R, D'Souza AR, Rorbach J, Kremer LS, Husain RA, et al. TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies. Am J Hum Genet. 2015;97(2):319–28 doi: 10.1016/j.ajhg.2015.06.011 26189817

19. Bohnsack MT, Sloan KE. The mitochondrial epitranscriptome: the roles of RNA modifications in mitochondrial translation and human disease. Cell Mol Life Sci. 2018;75(2):241–60 doi: 10.1007/s00018-017-2598-6 28752201

20. de Crecy-Lagard V, Boccaletto P, Mangleburg CG, Sharma P, Lowe TM, Leidel SA, et al. Matching tRNA modifications in humans to their known and predicted enzymes. Nucleic Acids Res. 2019;47(5):2143–59 doi: 10.1093/nar/gkz011 30698754

21. Jackman JE, Phizicky EM. tRNAHis guanylyltransferase adds G-1 to the 5' end of tRNAHis by recognition of the anticodon, one of several features unexpectedly shared with tRNA synthetases. RNA. 2006;12(6):1007–14 doi: 10.1261/rna.54706 16625026

22. Christian T, Gamper H, Hou YM. Conservation of structure and mechanism by Trm5 enzymes. RNA. 2013;19(9):1192–9 doi: 10.1261/rna.039503.113 23887145

23. Goto-Ito S, Ito T, M K, Bessho Y, Yokoyama S. Tertiary structure checkpoint at anticodon loop modification in tRNA functional maturation. Nat Struct Mol Biol. 2009;16:1109–15 doi: 10.1038/nsmb.1653 19749755

24. Zhou C, Huang RH. Crystallographic snapshots of eukaryotic dimethylallyltransferase acting on tRNA: insight into tRNA recognition and reaction mechanism. Proc Natl Acad Sci U S A. 2008;105(42):16142–7 doi: 10.1073/pnas.0805680105 18852462

25. Golovko A, Hjalm G, Sitbon F, Nicander B. Cloning of a human tRNA isopentenyl transferase. Gene. 2000;258(1–2):85–93 doi: 10.1016/s0378-1119(00)00421-2 11111046

26. Yevdakova NA, von Schwartzenberg K. Characterisation of a prokaryote-type tRNA-isopentenyltransferase gene from the moss Physcomitrella patens. Planta. 2007;226(3):683–95 doi: 10.1007/s00425-007-0516-0 17450376

27. Patil G, Nicander B. Identification of two additional members of the tRNA isopentenyltransferase family in Physcomitrella patens. Plant Mol Biol. 2013;82(4–5):417–26 doi: 10.1007/s11103-013-0072-x 23712255

28. Chen Y, Bai B, Yan H, Wen F, Qin D, Jander G, et al. Systemic disruption of the homeostasis of transfer RNA isopentenyltransferase causes growth and development abnormalities in Bombyx mori. Insect Mol Biol 2019;28(3):380–91 doi: 10.1111/imb.12561 30548717

29. Golovko A, Sitbon F, Tillberg E, Nicander B. Identification of a tRNA isopentenyltransferase gene from Arabidopsis thaliana. Plant Mol Biol. 2002;49(2):161–9 doi: 10.1023/a:1014958816241 11999372

30. Janner F, Vogeli G, Fluri R. The antisuppressor strain sin1 of Schizosaccharomyces pombe lacks the modification isopentenyladenosine in transfer RNA. J Mol Biol. 1980;139(2):207–19 doi: 10.1016/0022-2836(80)90305-8 7411631

31. Laten HM. Antisuppression of class I suppressors in an isopentenylated-transfer RNA deficient mutant of Saccharomyces cerevisiae. Curr Genet. 1984;8(1):29–32 doi: 10.1007/BF00405428 24177526

32. Dihanich ME, Najarian D, Clark R, Gillman EC, Martin NC, Hopper AK. Isolation and characterization of MOD5, a gene required for isopentenylation of cytoplasmic and mitochondrial tRNAs of Saccharomyces cerevisiae. Mol Cell Biol. 1987;7(1):177–84 doi: 10.1128/mcb.7.1.177 3031456

33. Rijal K, Maraia RJ, Arimbasseri AG. A methods review on use of nonsense suppression to study 3' end formation and other aspects of tRNA biogenesis. Gene. 2015;556(1):35–50 doi: 10.1016/j.gene.2014.11.034 25447915

34. Gillman EC, Slusher LB, Martin NC, Hopper AK. MOD5 translation initiation sites determine N6-isopentenyladenosine modification of mitochondrial and cytoplasmic tRNA. Mol Cell Biol. 1991;11(5):2382–90 doi: 10.1128/mcb.11.5.2382 1850093

35. Boguta M, Hunter LA, Shen WC, Gillman EC, Martin NC, Hopper AK. Subcellular locations of MOD5 proteins: mapping of sequences sufficient for targeting to mitochondria and demonstration that mitochondrial and nuclear isoforms commingle in the cytosol. Mol Cell Biol. 1994;14(4):2298–306 doi: 10.1128/mcb.14.4.2298 8139535

36. Tolerico LH, Benko AL, Aris JP, Stanford DR, Martin NC, Hopper AK. Saccharomyces cerevisiae Mod5p-II contains sequences antagonistic for nuclear and cytosolic locations. Genetics. 1999;151(1):57–75 9872948

37. Pratt-Hyatt M, Pai DA, Haeusler RA, Wozniak GG, Good PD, Miller EL, et al. Mod5 protein binds to tRNA gene complexes and affects local transcriptional silencing. Proc Natl Acad Sci U S A. 2013;110(33):E3081–9 doi: 10.1073/pnas.1219946110 23898186

38. Smaldino PJ, Read DF, Pratt-Hyatt M, Hopper AK, Engelke DR. The cytoplasmic and nuclear populations of the eukaryote tRNA-isopentenyl transferase have distinct functions with implications in human cancer. Gene. 2015;556(1):13–8 doi: 10.1016/j.gene.2014.09.049 25261850

39. Bertrand E, Houser-Scott F, Kendall A, Singer RH, Engelke DR. Nucleolar localization of early tRNA processing. Genes Dev. 1998;12(16):2463–8 doi: 10.1101/gad.12.16.2463 9716399

40. Thompson M, Haeusler RA, Good PD, Engelke DR. Nucleolar clustering of dispersed tRNA genes. Science. 2003;302(5649):1399–401. doi: 10.1126/science.1089814 14631041

41. Kessler AC, d'Almeida GS, Alfonzo JD. The role of intracellular compartmentalization on tRNA processing and modification. RNA biology. 2017:0

42. Cherkasova V, Bahler J, Bacikova D, Pridham K, Maraia RJ. Altered nuclear tRNA metabolism in La-deleted S. pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p. Mol Biol Cell. 2012;23:480–91 doi: 10.1091/mbc.E11-08-0732 22160596

43. Lamichhane TN, Blewett NH, Maraia RJ. Plasticity and diversity of tRNA anticodon determinants of substrate recognition by eukaryotic A37 isopentenyltransferases. RNA. 2011;17:1846–57 doi: 10.1261/rna.2628611 21873461

44. Lemieux J, Lakowski B, Webb A, Meng Y, Ubach A, Bussiere F, et al. Regulation of physiological rates in Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria. Genetics. 2001;159(1):147–57 11560893

45. Leung HC, Chen Y, Winkler ME. Regulation of substrate recognition by the MiaA tRNA prenyltransferase modification enzyme of Escherichia coli K-12. J Biol Chem. 1997;272(20):13073–83 doi: 10.1074/jbc.272.20.13073 9148919

46. Soderberg T, Poulter CD. Escherichia coli dimethylallyl diphosphate:tRNA dimethylallyltransferase: essential elements for recognition of tRNA substrates within the anticodon stem-loop. Biochemistry. 2000;39(21):6546–53 doi: 10.1021/bi992775u 10828971

47. Soderberg T, Poulter CD. Escherichia coli dimethylallyl diphosphate:tRNA dimethylallyltransferase: site-directed mutagenesis of highly conserved residues. Biochemistry. 2001;40(6):1734–40 doi: 10.1021/bi002149t 11327834

48. Chimnaronk S, Forouhar F, Sakai J, Yao M, Tron CM, Atta M, et al. Snapshots of dynamics in synthesizing N(6)-isopentenyladenosine at the tRNA anticodon. Biochemistry. 2009;48(23):5057–65 doi: 10.1021/bi900337d 19435325

49. Motorin Y, Bec G, Tewari R, Grosjean H. Transfer RNA recognition by the Escherichia coli delta2-isopentenyl-pyrophosphate:tRNA delta2-isopentenyl transferase: dependence on the anticodon arm structure. RNA. 1997;3(7):721–33 9214656

50. Sibler AP, Bordonne R, Dirheimer G, Martin R. [Primary structure of yeast mitochondrial tryptophan-tRNA capable of translating the termination U-G-A codon]. C R Seances Acad Sci D. 1980;290(11):695–8 6769601

51. Sprinzl M, Gauss DH. Compilation of tRNA sequences. Nucleic Acids Res. 1982;10(2):r1–55 7063409

52. Claros MG. MitoProt, a Macintosh application for studying mitochondrial proteins. Comput Appl Biosci. 1995;11(4):441–7 doi: 10.1093/bioinformatics/11.4.441 8521054

53. Fukasawa Y, Tsuji J, Fu SC, Tomii K, Horton P, Imai K. MitoFates: improved prediction of mitochondrial targeting sequences and their cleavage sites. Mol Cell Proteomics. 2015;14(4):1113–26 doi: 10.1074/mcp.M114.043083 25670805

54. Kosugi S, Hasebe M, Tomita M, Yanagawa H. Systematic identification of cell cycle-dependent yeast nucleocytoplasmic shuttling proteins by prediction of composite motifs. Proc Natl Acad Sci U S A. 2009;106(25):10171–6 doi: 10.1073/pnas.0900604106 19520826

55. Martin NC, Hopper AK. How single genes provide tRNA processing enzymes to mitochondria, nuclei and the cytosol. Biochimie. 1994;76(12):1161–7 doi: 10.1016/0300-9084(94)90045-0 7748951

56. Murawski M, Szczesniak B, Zoladek T, Hopper AK, Martin NC, Boguta M. maf1 mutation alters the subcellular localization of the Mod5 protein in yeast. Acta Biochim Pol. 1994;41(4):441–8 7732762

57. Eckers E, Cyrklaff M, Simpson L, Deponte M. Mitochondrial protein import pathways are functionally conserved among eukaryotes despite compositional diversity of the import machineries. Biol Chem. 2012;393(6):513–24 doi: 10.1515/hsz-2011-0255 22628314

58. Fukasawa Y, Oda T, Tomii K, Imai K. Origin and Evolutionary Alteration of the Mitochondrial Import System in Eukaryotic Lineages. Mol Biol Evol. 2017;34(7):1574–86 doi: 10.1093/molbev/msx096 28369657

59. Lamichhane TN, Mattijssen S, Maraia RJ. Human cells have a limited set of tRNA anticodon loop substrates of the tRNA isopentenyltransferase TRIT1 tumor suppressor. Mol Cell Biol. 2013;33:4900–8 doi: 10.1128/MCB.01041-13 24126054

60. Lamichhane TN, Blewett NH, Cherkasova VA, Crawford AK, Iben JR, Farabaugh PJ, et al. Lack of tRNA modification isopentenyl-A37 alters mRNA decoding and causes metabolic deficiencies in fission yeast. Mol Cell Biol. 2013;33 doi: 10.1128/MCB.00278-13 23716598:2918–29

61. Spinola M, Galvan A, Pignatiello C, Conti B, Pastorino U, Nicander B, et al. Identification and functional characterization of the candidate tumor suppressor gene TRIT1 in human lung cancer. Oncogene. 2005;24:5502–9 doi: 10.1038/sj.onc.1208687 15870694

62. Park JM, Intine RV, Maraia RJ. Mouse and Human La Proteins Differ in Kinase Substrate Activity and Activation Mechanism for tRNA Processing. Gene Expression. 2007;14:71–81 doi: 10.3727/105221607783417619 18257391

63. Spinola M, Falvella FS, Galvan A, Pignatiello C, Leoni VP, Pastorino U, et al. Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients' survival. Lung Cancer. 2007;55(3):271–7 doi: 10.1016/j.lungcan.2006.10.023 17145094

64. Yue Z, Li HT, Yang Y, Hussain S, Zheng CH, Xia J, et al. Identification of breast cancer candidate genes using gene co-expression and protein-protein interaction information. Oncotarget. 2016;7(24):36092–100 doi: 10.18632/oncotarget.9132 27150055

65. Chen S, Zheng Z, Tang J, Lin X, Wang X, Lin J. Association of polymorphisms and haplotype in the region of TRIT1, MYCL1 and MFSD2A with the risk and clinicopathological features of gastric cancer in a southeast Chinese population. Carcinogenesis. 2013;34(5):1018–24 doi: 10.1093/carcin/bgt010 23349019

66. Basi G, Schmid E, Maundrell K. TATA box mutations in the Schizosaccharomyces pombe nmt1 promoter affect transcription efficiency but not the transcription start point or thiamine repressibility. Gene. 1993;123(1):131–6 doi: 10.1016/0378-1119(93)90552-e 8422997

67. Forsburg SL. Comparison of Schizosaccharomyces pombe expression systems. Nucleic Acids Res. 1993;21(12):2955–6 doi: 10.1093/nar/21.12.2955 8332516

68. Slusher LB, Gillman EC, Martin NC, Hopper AK. mRNA leader length and initiation codon context determine alternative AUG selection for the yeast gene MOD5. Proc Natl Acad Sci U S A. 1991;88(21):9789–93 doi: 10.1073/pnas.88.21.9789 1946403

69. Auffinger P, Westhof E. Singly and bifurcated hydrogen-bonded base-pairs in tRNA anticodon hairpins and ribozymes. J Mol Biol. 1999;292(3):467–83 doi: 10.1006/jmbi.1999.3080 10497015

70. Olejniczak M, Uhlenbeck OC. tRNA residues that have coevolved with their anticodon to ensure uniform and accurate codon recognition. Biochimie. 2006;88(8):943–50 doi: 10.1016/j.biochi.2006.06.005 16828219

71. Chan PP, Lowe TM. GtRNAdb 2.0: an expanded database of transfer RNA genes identified in complete and draft genomes. Nucleic Acids Res. 2015;44(D1) doi: 10.1093/nar/gkv1309 26673694:44(D1):D184–9

72. Hamada M, Huang Y, Lowe TM, Maraia RJ. Widespread Use of TATA Elements in the Core Promoters for RNA Polymerases III, II, and I in Fission Yeast. Mol Cell Biol. 2001;21(20):6870–81 doi: 10.1128/MCB.21.20.6870-6881.2001 11564871

73. Forsburg SL. The best yeast? Trends Genet. 1999;15(9):340–4 doi: 10.1016/s0168-9525(99)01798-9 10461200

74. Miyauchi K, Kimura S, Suzuki T. A cyclic form of N6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification. Nat Chem Biol. 2013;9(2):105–11 doi: 10.1038/nchembio.1137 23242255

75. Rojas-Benitez D, Thiaville PC, de Crecy-Lagard V, Glavic A. The Levels of a Universally Conserved tRNA Modification Regulate Cell Growth. J Biol Chem. 2015;290(30):18699–707 doi: 10.1074/jbc.M115.665406 26063805

76. Maraia RJ, Arimbasseri AG. Factors That Shape Eukaryotic tRNAomes: Processing, Modification and Anticodon-Codon Use. Biomolecules. 2017;7(1)

77. Mattijssen S, Gaidamakov S, Maraia RJ. A mouse model of human tRNA isopentenyltransferase-1 deficiency. Forthcoming. 2020:Forthcoming

78. Benko AL, Vaduva G, Martin NC, Hopper AK. Competition between a sterol biosynthetic enzyme and tRNA modification in addition to changes in the protein synthesis machinery causes altered nonsense suppression. Proc Natl Acad Sci U S A. 2000;97(1):61–6 doi: 10.1073/pnas.97.1.61 10618371

79. Helm M, Alfonzo JD. Posttranscriptional RNA Modifications: Playing Metabolic Games in a Cell’s Chemical Legoland. Chem Biol. 2014;21(2):174–85 doi: 10.1016/j.chembiol.2013.10.015 24315934

80. Maraia RJ, Iben JR. Different types of secondary information in the genetic code. RNA. 2014;20(7):977–84 doi: 10.1261/rna.044115.113 24935971

81. Li JM, Hopper AK, Martin NC. N2,N2-dimethylguanosine-specific tRNA methyltransferase contains both nuclear and mitochondrial targeting signals in Saccharomyces cerevisiae. J Cell Biol. 1989;109(4 Pt 1):1411–9 doi: 10.1083/jcb.109.4.1411 2677019

82. Ellis SR, Hopper AK, Martin NC. Amino-terminal extension generated from an upstream AUG codon increases the efficiency of mitochondrial import of yeast N2,N2-dimethylguanosine-specific tRNA methyltransferases. Mol Cell Biol. 1989;9(4):1611–20 doi: 10.1128/mcb.9.4.1611 2657400

83. Machnicka MA, Olchowik A, Grosjean H, Bujnicki JM. Distribution and frequencies of post-transcriptional modifications in tRNAs. RNA biology. 2014;11(12):1619–29 doi: 10.4161/15476286.2014.992273 25611331

84. Bullerwell CE, Leigh J, Forget L, Lang BF. A comparison of three fission yeast mitochondrial genomes. Nucleic Acids Res. 2003;31(2):759–68 doi: 10.1093/nar/gkg134 12527786

85. Machnicka MA, Milanowska K, Osman Oglou O, Purta E, Kurkowska M, Olchowik A, et al. MODOMICS: a database of RNA modification pathways—2013 update. Nucleic Acids Res. 2013;41(Database issue):D262–7 doi: 10.1093/nar/gks1007 23118484

86. Jia W, Higgs PG. Codon usage in mitochondrial genomes: distinguishing context-dependent mutation from translational selection. Mol Biol Evol. 2008;25(2):339–51 doi: 10.1093/molbev/msm259 18048402

87. Yokoyama S, Nishimura S. Modified Nucleosides and Codon Recognition. tRNA: Structure, Biosynthesis and Function. Wash., D.C.: ASM Press; 1995. p. 207–23.

88. Jackman JE, Montange RK, Malik HS, Phizicky EM. Identification of the yeast gene encoding the tRNA m1G methyltransferase responsible for modification at position 9. RNA. 2003;9(5):574–85 doi: 10.1261/rna.5070303 12702816

89. Hofmann J, Schumann G, Borschet G, Gosseringer R, Bach M, Bertling WM, et al. Transfer RNA genes from Dictyostelium discoideum are frequently associated with repetitive elements and contain consensus boxes in their 5' and 3'-flanking regions. J Mol Biol. 1991;222(3):537–52 doi: 10.1016/0022-2836(91)90495-r 1660925

90. Arimbasseri AG, Blewett NH, Iben JR, Lamichhane TN, Cherkasova V, Hafner M, et al. RNA polymerase III output is functionally linked to tRNA dimethyl-G26 modification. PLoS Genetics. 2015; doi: 10.1371/journal.pgen.1005671 26720005

91. Steinberg S, Cedergren R. A correlation between N2-dimethylguanosine presence and alternate tRNA conformers. RNA. 1995;1(9):886–91 8548653

92. Martin RP, Sibler AP, Gehrke CW, Kuo K, Edmonds CG, McCloskey JA, et al. 5-[[(carboxymethyl)amino]methyl]uridine is found in the anticodon of yeast mitochondrial tRNAs recognizing two-codon families ending in a purine. Biochemistry. 1990;29(4):956–9 doi: 10.1021/bi00456a016 2187534

93. Johnson PF, Abelson J. The yeast tRNATyr gene intron is essential for correct modification of its tRNA product. Nature. 1983;302(5910):681–7 doi: 10.1038/302681a0 6339954

94. Heyer WD, Thuriaux P, Kohli J, Ebert P, Kersten H, Gehrke C, et al. An antisuppressor mutation of Schizosaccharomyces pombe affects the post-transcriptional modification of the "wobble" base in the anticodon of tRNAs. J Biol Chem. 1984;259(5):2856–62 6559822

95. Chittum HS, Baek HJ, Diamond AM, Fernandez-Salguero P, Gonzalez F, Ohama T, et al. Selenocysteine tRNA[Ser]Sec levels and selenium-dependent glutathione peroxidase activity in mouse embryonic stem cells heterozygous for a targeted mutation in the tRNA[Ser]Sec gene. Biochemistry. 1997;36(28):8634–9 doi: 10.1021/bi970608t 9214310

96. Johansson MJ, Esberg A, Huang B, Bjork GR, Bystrom AS. Eukaryotic wobble uridine modifications promote a functionally redundant decoding system. Mol Cell Biol. 2008;28(10):3301–12 doi: 10.1128/MCB.01542-07 18332122

97. Mattijssen S, Arimbasseri AG, Iben JR, Gaidamakov S, Lee J, Hafner M, et al. LARP4 mRNA codon-tRNA match contributes to LARP4 activity for ribosomal protein mRNA poly(A) tail length protection. Elife. 2017;6

98. Bruni F, Gramegna P, Oliveira JM, Lightowlers RN, Chrzanowska-Lightowlers ZM. REXO2 is an oligoribonuclease active in human mitochondria. PLoS One. 2013;8(5):e64670 doi: 10.1371/journal.pone.0064670 23741365

99. Intine RV, Dundr M, Vassilev A, Schwartz E, Zhao Y, Depamphilis ML, et al. Nonphosphorylated human La antigen interacts with nucleolin at nucleolar sites involved in rRNA biogenesis. Mol Cell Biol. 2004;24:10894–904. doi: 10.1128/MCB.24.24.10894-10904.2004 15572691

100. Leonard G. Davis MDDaJFB. Basic Methods in Molecular Biology: Elsevier; 1986. 388 p.

101. Zur H, Tuller T. New universal rules of eukaryotic translation initiation fidelity. PLoS computational biology. 2013;9(7):e1003136 doi: 10.1371/journal.pcbi.1003136 23874179

102. Hamilton R, Watanabe CK, de Boer HA. Compilation and comparison of the sequence context around the AUG startcodons in Saccharomyces cerevisiae mRNAs. Nucleic Acids Res. 1987;15(8):3581–93 doi: 10.1093/nar/15.8.3581 3554144

103. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987;15(20):8125–48 doi: 10.1093/nar/15.20.8125 3313277

104. McIlwain SJ, Peris D, Sardi M, Moskvin OV, Zhan F, Myers KS, et al. Genome Sequence and Analysis of a Stress-Tolerant, Wild-Derived Strain of Saccharomyces cerevisiae Used in Biofuels Research. G3 (Bethesda). 2016;6(6):1757–66 doi: 10.1534/g3.116.029389 27172212

105. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet. 1999;23(2):147 doi: 10.1038/13779 10508508

106. Kohli J, Munz P, Soll D. Informational suppression, transfer RNA, and intergenic conversion. In: Nasim A, Young P, Johnson BF, editors. Molecular Biology of the Fission Yeast. Cell Biology. San Diego: Academic Press, Inc.; 1989. p. 75–96.

107. Hamada M, Sakulich AL, Koduru SB, Maraia R. Transcription termination by RNA polymerase III in fission yeast: A genetic and biochemical model system. J Biol Chem. 2000;275:29076–81 doi: 10.1074/jbc.M003980200 10843998

108. Schon A, Bock A, Ott G, Sprinzl M, Soll D. The selenocysteine-inserting opal suppressor serine tRNA from E. coli is highly unusual in structure and modification. Nucleic Acids Res. 1989;17(18):7159–65 doi: 10.1093/nar/17.18.7159 2529478

109. Bonitz SG, Berlani R, Coruzzi G, Li M, Macino G, Nobrega FG, et al. Codon recognition rules in yeast mitochondria. Proc Natl Acad Sci U S A. 1980;77(6):3167–70 doi: 10.1073/pnas.77.6.3167 6997870

110. Kerscher S, Durstewitz G, Casaregola S, Gaillardin C, Brandt U. The complete mitochondrial genome of yarrowia lipolytica. Comp Funct Genomics. 2001;2(2):80–90 doi: 10.1002/cfg.72 18628906

111. Zivanovic Y, Wincker P, Vacherie B, Bolotin-Fukuhara M, Fukuhara H. Complete nucleotide sequence of the mitochondrial DNA from Kluyveromyces lactis. FEMS Yeast Res. 2005;5(4–5):315–22 doi: 10.1016/j.femsyr.2004.09.003 15691736

112. Chan PP & Lowe TM. tRNAscan-SE: Searching for tRNA Genes in Genomic Sequences. Methods Mol Biol. 2019; 1962:1–14 doi: 10.1007/978-1-4939-9173-0_1 31020551

Článek vyšel v časopise

PLOS Genetics

2020 Číslo 4

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Zvyšte si kvalifikaci online z pohodlí domova

Antiseptika a prevence ve stomatologii
nový kurz
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Diagnostika a léčba deprese pro ambulantní praxi
Autoři: MUDr. Jan Hubeňák, Ph.D

Snímatelné zubní náhrady a fixační krémy
Autoři: doc. MUDr. Hana Hubálková, Ph.D.

Nová éra v léčbě migrény
Autoři: MUDr. Eva Medová, MUDr. Tomáš Nežádal, Ph.D.

Význam nutraceutik u kardiovaskulárních onemocnění

Všechny kurzy
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se